4-Dimethyl amino pyridine (C7H10N2) belongs to the category of 4-position substitution derivatives of pyridine. It is widely used as a hypemucleophilic acylation catalyst. 4-Dimethyl amino pyridine is a highly efficient catalyst for acylation reactions as compared to other traditional acylation catalytic agents due to its effectiveness, cost efficiency and long time efficiency property.
Several processes are known for the preparation of 4-dimethyl amino pyridine. The known processes differ from each other with respect to the different chemical processes employed.
U.S. Pat. No. 4,220,785 to Oude Alink, et al. discloses the preparation of substituted pyridines by reacting aldehydes, amines, and lower carboxylic acids, such as acetic acid, in the presence of oxygen. The N-substituted pyridinium salts formed are then converted to pyridines by thermal dealkylation.
U.S. Pat. No. 4,158,093 to Baily et al. discloses a process in which a 4-substituted pyridine base is first quaternized with 2-vinyl pyridine in the presence of a strong acid to give a pyridyl ethyl quaternery salt. This activated quaternery salt is subjected to nucleophilic substitution at the 4-position and then dequaternized in the presence of sodium hydroxide.
U.S. Pat. No. 4,672,121 and U.S. Pat. No. 4,772,713 to Nummy et al. disclose a process for preparing a 4-substituted pyridine product from a starting pyridine substituted in the 4-position by a leaving group susceptible to nucleophilic displacement when the starting pyridine is quaternized. The process comprises quaternizing the starting pyridine, with acrylamide, N-monoalkylacrylamide or N-dialkylacrylamide under effective acidic conditions; subjecting the resultant, corresponding quaternized starting pyridine to a nucleophilic displacement reaction with a reagent that reacts to produce the corresponding 4-substituted pyridine; and dequatemizing the latter under effective basic conditions to liberate the desired 4substituted pyridine product.
An article authored by Xi Guan Gen et al. published in Chemical Reagent, 1998, 20(2), 119-120, discloses a process, in which pyridine is quaternized with thionyl chloride (SOCl2) in the presence of ethyl acetate, and then aminating the resulting salt, N-[4-pyridyl]pyridinium chloride hydrochloride, with N,N-dimethyl formamide. The resulting reaction mass is hydrolysed in the presence of a base, and extracted with chloroform. This is an improved process compared to the one disclosed in the Chinese article authored by Li Bao Qing, the Department of Chemical Industry, Costume Academy, Beijing 100029.
A significant problem in the above-described processes is that of the formation of highly hazardous and unsafe by-products like hydrogen cyanide and sodium cyanide, which are very unsafe to handle in the laboratory as well as in a commercial-scale manufacturing process. Also, costlier raw materials like cyanopyridine and vinyl pyridine were used in the processes.
Most of these problems have been well addressed by Xi Guan Gen et al. However, the processing of the reaction mass involves many undesirable steps. Also the product quality and yield are not found to be satisfactory, so the process was not found suitable for industrial applications.
Therefore there is a need for an improved process for producing 4-dimethyl amino pyridine especially suitable for large-scale manufacture. Large-scale manufacturing requires the production of the compound in a cost efficient manner, resulting in a need for an improved process for producing 4-dimethyl amino pyridine with high purity and with a better yield.
Another concern with respect to the present invention is to provide a process for producing 4-DMAP where little or no hazardous byproducts are formed so that the process is suitable for industrial use. Also, the known methods do not address the ability to recover and recycle the byproducts.
Known processes are not techno-economically viable. The product quality/yield could be higher, thus making the processes unviable for industrial application. It is therefore desirable to develop a suitable process to address the above-mentioned problems in the known process.